Long-term safety of dichloroacetate in congenital lactic acidosis
Long-term safety of dichloroacetate in congenital lactic acidosis
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DOI：
10.1016/j.ymgme.2013.03.019
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发表时间：
2013-06-01
影响因子：
3.8
通讯作者：
Stacpoole, Peter W.
中科院分区：
文献类型：
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作者：
Abdelmalak, Monica;Lew, Alicia;Stacpoole, Peter W.
我们跟踪观察了8名患者(4名男性)，他们接受口服二氯乙酸酯(DCA；12.5 mg/kg/12h)治疗9.7~16.5年，这些患者的丙酮酸脱氢酶复合体(PDC)的El Et亚单位(PDC)或呼吸链复合体I(I)、IV(3)或I+IV(1)存在生化和/或分子遗传学缺陷。所有受试者最初都参加了DCA的随机对照试验，并继续进行开放标签的慢性安全性研究。患者(1名成人)在开始使用DCA时年龄从3.5岁到40.2岁，现在是16.9岁到49.9岁(平均+/-SD：23.5+/-10.9岁)。受试者的年龄和性别均为正常或低于正常体重。3例PDC缺陷患者不食用高脂(生酮)饮食。DCA维持正常的血乳酸浓度，即使在基本上不受限制的饮食中PDC缺乏的儿童也是如此。血液学、电解质、肾脏和肝脏状况保持稳定。神经传导没有改变或轻度下降，导致3例DCA减少或暂时停止，尽管没有出现周围神经病的症状恶化。我们的结论是，对于先天性乳酸酸中毒的患者，长期给予DCA的耐受性通常很好，并有效地维持正常的血乳酸水平，即使是在PDC缺陷而不食用严格的生酮饮食的儿童。(C)2013 Elsevier Inc.保留所有权利。
We followed 8 patients (4 males) with biochemically and/or molecular genetically proven deficiencies of the El et subunit of the pyruvate dehydrogenase complex (PDC; 3 patients) or respiratory chain complexes I (I patient), IV (3 patients) or I + IV (1 patient) who received oral dichloroacetate (DCA; 12.5 mg/kg/12 h) for 9.7 to 16.5 years. All subjects originally participated in randomized controlled trials of DCA and were continued on an open-label chronic safety study. Patients (1 adult) ranged in age from 3.5 to 40.2 years at the start of DCA administration and are currently aged 16.9 to 49.9 years (mean +/- SD: 23.5 +/- 10.9 years). Subjects were either normal or below normal body weight for age and gender. The 3 PDC deficient patients did not consume high fat (ketogenic) diets. DCA maintained normal blood lactate concentrations, even in PDC deficient children on essentially unrestricted diets. Hematological, electrolyte, renal and hepatic status remained stable. Nerve conduction either did not change or decreased modestly and led to reduction or temporary discontinuation of DCA in 3 patients, although symptomatic worsening of peripheral neuropathy did not occur. We conclude that chronic DCA administration is generally well-tolerated in patients with congenital causes of lactic acidosis and is effective in maintaining normal blood lactate levels, even in PDC-deficient children not consuming strict ketogenic diets. (C) 2013 Elsevier Inc. All rights reserved.